Biocidal compositions and use thereof containing a synergistic mixture of tetraalkyl phosphonium halide and n-alkyl dimethylbenzyl ammonium chloride

ABSTRACT

A bactericidal composition and method for inhibiting and controlling the growth of the capsulated, facultative bacterium, Klebsiella pneumoniae, are disclosed. The composition comprises an amount, effective for the intended purpose, of n-alkyl dimethyl benzyl ammonium chloride and tetraalkyl phosphonium halide. The method comprises administering between about 0.1 to about 200 parts of this combined treatment (based on one million parts of the desired aqueous system) to the particular water containing system for which treatment is desired.

BACKGROUND OF THE INVENTION

The formation of slimes by microorganisms is a problem that isencountered in many aqueous systems. For example, the problem is notonly found in natural waters such as lagoons, lakes, ponds, etc., andconfined waters as in pools, but also in such industrial systems ascooling water systems, air washer systems and pulp and paper millsystems. All possess conditions which are conducive to the growth andreproduction of slime-forming microorganisms. In both once-through andrecirculating cooling systems, for example, which employ largequantities of water as a cooling medium, the formation of slime bymicroorganisms is an extensive and constant problem.

Airborne organisms are readily entrained in the water from coolingtowers and find this warm medium in ideal environment for growth andmultiplication. Aerobic and heliotropic organisms fluorish on the towerproper while other organisms colonize and grow in such areas as thetower sump and the piping and passages of the cooling system. The slimeformation not only aids in the deterioration of the tower structure inthe case of wooden towers, but also promotes corrosion when it depositson metal surfaces. Slime carried through the cooling system plugs andfouls lines, valves, strainers, etc., and deposits on heat exchangesurfaces. In the latter case, the impedance of heat transfer can greatlyreduce the efficiency of the cooling system.

In pulp and paper mill systems, slime formed by microorganisms iscommonly encountered and causes fouling, plugging, or corrosion of thesystem. The slime also becomes entrained in the paper produced to causebreakouts on the paper machines, which results in work stoppages and theloss of production time. The slime is also responsible for unsightlyblemishes in the final product, which result in rejects and wastedoutput.

The previously discussed problems have resulted in the extensiveutilization of biocides in cooling water and pulp and paper millsystems. Materials which have enjoyed widespread use in suchapplications include chlorine, chlorinated phenols, organobromines, andvarious organo-sulfur compounds. All of these compounds are generallyuseful for this purpose but each is attended by a variety ofimpediments. For example, chlorination is limited both by its specifictoxicity for slime-forming organisms at economic levels and by thetendency of chlorine to react, which results in the expenditure of thechlorine before its full biocidal function is achieved. Other biocidesare attended by odor problems and hazards in respect to storage, use orhandling which limit their utility. To date, no one compound or type ofcompound has achieved a clearly established predominance in respect tothe applications discussed. Likewise, lagoons, ponds, lakes, and evenpools, either used for pleasure purposes or used for industrial purposesfor the disposal and storage of industrial wastes, become, during thewarm weather, beseiged by slime due to microorganisms growth andreproduction. In the case of the recreational areas the problem ofinfection is obvious. In the case of industrial storage or disposal ofindustrial materials, the microorganisms cause additional problems whichmust be eliminated prior to the material's use or disposal of the waste.

Naturally, economy is a major consideration in respect to all of thesebiocides. Such economic considerations attach to both the cost of thebiocide and the expense of its application. The cost performance indexof any biocide is derived from the basic cost of the material, itseffectiveness per unit of weight, the duration of its biocidal orbiostatic effect in the system treated, and the ease and frequency ofits addition to the system treated. To date, none of the commerciallyavailable biocides has exhibited a prolonged biocidal effect. Instead,their effectiveness is rapidly reduced as the result of exposure tophysical conditions such as temperature, association with ingredientscontained by the system toward which they exhibit an affinity orsubstantivity, etc., with a resultant restriction or elimination oftheir biocidal effectiveness, or by dilution.

As a consequence, the use of such biocides involves their continuous orfrequent addition to systems to be treated and their addition tomultiple points or zones in the systems to be treated. Accordingly, thecost of the biocide and the labor cost of such means of applying it areconsiderable. In other instances, the difficulty of access to the zonein which slime formation is experienced precludes the effective use of abiocide. For example, if in a particular system there is no access to anarea at which slime formation occurs the biocide can only be applied ata point which is upstream in the flow system. However, the physical orchemical conditions, e.g., chemical reactivity, thermal degradation,etc., which exist between the point at which the biocide may be added tothe system and the point at which its biocidal effect is desired renderthe effective use of a biocide impossible.

Similarly, in a system experiencing relatively slow flow, such as apaper mill, if a biocide is added at the beginning of the system, itsbiocidal effect may be completely dissipated before it has reached allof the points at which this effect is desired or required. As aconsequence, the biocide must be added at multiple points, and even thena diminishing biocidal effect will be experienced between one point ofaddition to the system and the next point downstream at which thebiocides may be added. In addition to the increased cost of utilizingand maintaining multiple feed points, gross ineconomies in respect tothe cost of the biocide are experienced. Specifically, at each point ofaddition, an excess of the biocide is added to the system in order tocompensate for that portion of the biocide which will be expended inreacting with other constituents present in the system or experiencephysical changes which impair its biocidal activity.

SUMMARY OF THE INVENTION

The biocidal compositions of the present invention comprises, as activeingredients, (1) a tetraalkyl phosphonium halide compound, (hereinafter"TPH") and (2) an n-alkyl (50% C₁₄, 40% C₁₂, 10% C₁₆) dimethyl benzylammonium chloride (hereinafter "quat").

PRIOR ART

The specific TPH herein preferred for use is tri-n-butyl tetradecylphosphonium chloride (hereinafter "TPC"). This particular tetraalkylphosphonium halide is commercially available from Ciba-Geigy under thetrademark "Belclene 350" and is touted as a "broad spectrum biocidespecifically developed for the control of microbiological fouling incooling water systems." Use of the TPH compound in a biocidalcomposition is disclosed in U.S. Pat. No. 4,725,587 (Whitekettle et al),of common assignment herewith.

N-alkyl (C₁₂ -C₁₈) dimethyl benzyl ammonium choride is listed at 21 CFR176.300 as being a slimicide that may be safely used in the manufactureof paper and paperboard products that contact food. Use of the quatcompounds in various biocidal compositions is also disclosed in U.S.Pat. No. 3,934,025 (Swered et al); U.S. Pat. No. 3,827,873 (Shema etal); and U.S. Pat. No. 3,881,008 (Shema et al).

Although both quat and TPH are known biocidal compounds theirsynergistic effect upon combination has not previously been disclosed.

DETAILED DESCRIPTION OF THE INVENTION

Surprisingly, the present inventors have found that mixtures of atetraalkyl phosphonium halide compound, (TPH) and an n-alkyl (40% C₁₂,50% C₁₄, 10% C₁₆) dimethyl benzyl ammonium chloride (quat) areespecially efficacious in controlling the growth of bacterial microbes,specifically the Klebsiella pneumoniae species. This particular speciesis a member of the capsulated, facultative class of bacteria and isgenerally present in air, water, and soil. These bacteria continuallycontaminate open cooling systems and pulping and papermaking systems andare among the most common slime formers. The slime may be viewed asbeing a mass of agglomerated cells struck together by the cementingaction of the gelatinous polysaccharide or proteinaceous secretionsaround each cell. The slimy mass entraps other debris, restricts waterflow and heat transfer, and may serve as a site for corrosion.

The fact that the Klebsiella species used in the tests is a facultativespecies is important as, by definition, such bacteria may thrive undereither aerobic or anaerobic conditions. Accordingly, by reason ofdemonstrated efficacy in the growth inhibition of this particularspecies, one can expect similar growth inhibition attributes when otheraerobic or anaerobic bacterial species are encountered. It is alsoexpected that these compositions will exhibit similar growth inhibitionattributes when fungi and algae species are encountered.

Quat is commercially available from various sources. For instance, it issold under the trademark "Maquat 1412" from Mason Chemical Co., "Onyx8358" from Onyx Chemical Co., or "Hyamine 3500" by Lonza Inc.

As noted above, TPC is available from Ciba-Geigy and is sold under thetrademark "Belclene 350". The physical properties of "Belclene 350" arereported as being:

Appearance: Clear, colorless liquid

Specific gravity at 20° C.: 0.96

pH: 7.0-8.0

Boiling point: 100° C.

Freezing point: -8 to -10° C.

Viscosity: 50-80 cP

Odor: slight

Solubility:

Water: Completely miscible in all proportions

Methanol: Greater than 50%

Isopropanol: Greater than 50%

Ethylene Glycol: Greater than 50%

In accordance with the present invention, the combined TPH:quattreatment may be added to the desired aqueous system in need of biocidaltreatment, in an amount of from about 0.1 to about 200 parts of thecombined treatment to one million parts (by weight) of the aqueousmedium. Preferably, about 5 to about 50 parts of the combined treatmentper one million parts (by weight) of the aqueous medium is added.

The combined treatment is added, for example, to cooling water systems,paper and pulp mill systems, pools, ponds, lagoons, lakes, etc., tocontrol the formation of bacterial microorganisms, which may becontained by, or which may become entrained in, the system to betreated. It has been found that the TPH:quat compositions and methods ofutilization of the treatment are efficacious in controlling thefacultative bacterium, Klebsiella pneumoniae, which may populate thesesystems. It is thought that the combined treatment composition andmethod of the present invention will also be efficacious in inhibitingand controlling all types of aerobic and anaerobic bacteria.

Surprisingly, it has been found that when the TPH:quat ingredients aremixed, in certain instances, the resulting mixtures possess a higherdegree of bactericidal activity than that of the individual ingredientscomprising the mixture. Accordingly, it is possible to produce a highlyefficacious bactericide. Because of the enhanced activity of themixture, the total quantity of the bacterial treatment may be reduced.In addition, the high degree of bactericidal effectiveness which isprovided by each of the ingredients may be exploited without use ofhigher concentrations of each.

The following experimental data were developed. It is to be rememberedthat the following examples are to be regarded solely as beingillustrative, and not as restricting the scope of the invention.

DESCRIPTION OF PREFERRED EMBODIMENT

TPC and quat were added in varying ratios and over a wide range ofconcentrations to a liquid nutrient medium which was subsequentlyinoculated with a standard volume of a suspension of the facultativebacterium Klebsiella pneumoniae. Growth was measured by determining theamount of radioactivity accumulated by the cells when ¹⁴ C glucose wasadded as the sole source of carbon in the nutrient medium. The effect ofthe biocide chemicals, alone and in combination, is to reduce the rateand amount of ¹⁴ C incorporation into the cells during incubation, ascompared to controls not treated with the chemicals. Additions of thebiocides, alone and in varying combinations and concentrations, weremade according to the accepted "checkerboard" technique described by M.T. Kelley and J. M. Matsen, Antimicrobial Agents and Chemotherapy. 9:440 (1976). Following a two hour incubation, the amount of radioactivityincorporated in the cells was determined by counting (¹⁴ C liquidscintillation procedures) for all treated and untreated samples. Thepercent reduction of each treated sample was calculated from therelationship: ##EQU1##

Plotting the % reduction of ¹⁴ C level against the concentration of eachbiocide acting alone results in a dose-response curve, from which thebiocide dose necessary to achieve any given % reduction can beinterpolated.

Synergism was determined by the method of calculation described by F. C.Kull, P. C. Eisman, H. D. Sylwestrowicz and R. L. Mayer, AppliedMicrobiology 9:538 (1961) using the relationship. ##EQU2## where: Q_(a)=quantity of compound A, acting alone, producing an end point

Q_(b) =quantity of compound B, acting alone, producing an end point

Q_(A) =quantity of compound A in mixture, producing an end point

Q_(B) =quantity of compound B in mixture, producing an end point

The end point used in the calculations is the % reduction caused by eachmixture of A and B. Q_(A) and Q_(B) are the individual concentrations inthe A/B mixture causing a given % reduction. Q_(a) and Q_(b) aredetermined by interpolation from the respective doseresponse curves of Aand B as those concentrations of A and B acting alone which produce thesame % reduction as each specific mixture produced.

Dose-response curves for each active acting alone were determined bylinear regression analysis of the dose-response data. After linearizingthe data, the contributions of each biocide component in the biocidemixtures to the inhibition of radioisotope uptake were determined byinterpolation with the dose-response curve of the respective biocide.If, for example, quantities of Q_(A) plus Q_(B) are sufficient to give a50% reduction in ¹⁴ C content, Q_(a) and Q_(b) are those quantities of Aor B acting alone, respectively, found to give 50% reduction in ¹⁴ Ccontent. A synergism index (SI) is calculated for each combination of Aand B.

Where the SI is <1, synergism exists. Where the SI=1, additivity exists.Where SI>1, antagonism exists.

The data in the following tables come from treating Klebsiellapneumoniae, a common nuisance bacterial type found in industrial coolingwaters and in pulping and paper making systems, with varying ratios andconcentrations of quat and TPC. Shown for each combination is the %reduction of ¹⁴ C content (% I), the calculated SI, and the weight ratioof TPC to quat.

                  TABLE I                                                         ______________________________________                                        Belclene 350 vs. Quat                                                                           Ratio                                                       Belclene**                                                                              Quat**  Belclene:Quat % I  SI                                       ______________________________________                                        0         20      0:100         96                                            0         10      0:100         92                                            0         7.5     0:100         89                                            0         5       0:100         47                                            0         3.75    0:100         39                                            0         2.5     0:100          0                                            0         1.25    0:100          0                                            0         0.625   0:100          0                                            100       0       100:0         94                                            80        0       100:0         86                                            50        0       100:0         68                                            40        0       100:0         52                                            25        0       100:0         29                                            20        0       100:0          3                                            100       20       5:1          99   2.33                                     100       10       10:1         98   1.73                                     100       7.5     13.3:1        98   1.56                                     100       5        20.1         98   1.38                                     100       3.75    26.7:1        98   1.29                                     100       2.5      40:1         98   1.20                                     100       1.25     80:1         97   1.13                                     100       0.625   160:1         98   1.07                                     80        20       4:1          99   2.13                                     80        10       8:1          98   1.53                                     80        7.5     10.7:1        98   1.35                                     80        5        16:1         98   1.20                                     80        3.75    21.3:1        97   1.10                                     80        2.5      32:1         95   1.05                                     80        1.25     64:1         95   0.96                                     80        0.625   128:1         94   0.93*                                    50        20       2.5:1        98   1.94                                     50        10       5:1          98   1.22                                     50        7.5      6.7:1        98   1.05                                     50        5        10:1         93   0.94                                     50        3.75    13.3:1        94   0.84*                                    50        2.5      20:1         89   0.81*                                    50        1.25     40:1         87   0.74*                                    50        0.625    80:1         85   0.71*                                    40        20       2:1          98   1.84                                     40        10       4:1          98   1.12                                     40        7.5      5.3:1        97   0.95                                     40        5        8:1          91   0.88*                                    40        3.75    10.7:1        91   0.78*                                    40        2.5      16:1         84   0.75*                                    40        1.25     32:1         69   0.87*                                    40        0.625    64:1         67   0.80*                                    25        20      1.25:1        97   1.67                                     25        10       2.5:1        97   0.97                                     25        7.5      3.3:1        96   0.80*                                    25        5        5:1          89   0.72*                                    25        3.75     6.7:1        88   0.65*                                    25        2.5      10:1         76   0.66*                                    25        1.25     20:1         60   0.72*                                    25        0.625    40:1         51   0.73*                                    20        20       1:1          99   1.53                                     20        10       2:1          96   0.92*                                    20        7.5      2.7:1        96   0.75*                                    20        5        4:1          86   0.71*                                    20        3.75    5.33:1        82   0.65*                                    20        2.5      8:1          57   0.85*                                    20        1.25     16:1         19   1.29                                     20        0.625    32:1         19   1.08                                     ______________________________________                                    

                  TABLE II                                                        ______________________________________                                        Belclene 350 vs. Quat                                                         ppm       ppm     Ratio                                                       Belclene**                                                                              Quat**  Belclene:Quat % I  SI                                       ______________________________________                                        0         20      0:100         98                                            0         10      0:100         91                                            0         7.5     0:100         91                                            0         5       0:100         56                                            0         3.75    0:100         41                                            0         2.5     0:100         0                                             0         1.25    0:100         0                                             0         0.625   0:100         0                                             100       0       100:0         93                                            80        0       100:0         91                                            50        0       100:0         72                                            40        0       100:0         66                                            25        0       100:0         29                                            20        0       100:0         20                                            100       20       5:1          99   2.73                                     100       10       10:1         99   1.90                                     100       7.5     13.3:1        98   2.17                                     100       5        20:1         98   1.51                                     100       3.75    26.7:1        98   1.40                                     100       2.5      40:1         97   1.32                                     100       1.25     8:1          97   1.22                                     100       0.625   160:1         97   1.16                                     80        20       4:1          99   2.52                                     80        10       8:1          99   1.68                                     80        7.5     10.7:1        98   1.49                                     80        5        16:1         98   1.29                                     80        3.75    21.3:1        97   1.20                                     80        2.5      32:1         96   1.12                                     80        1.25     64:1         96   1.01                                     80        0.625   128:1         96   0.96                                     50        20       2.5:1        99   2.20                                     50        10       5:1          98   1.38                                     50        7.5      6.7:1        99   1.16                                     50        5        10:1         93   1.06                                     50        3.75    13.3:1        96   0.88*                                    50        2.5      20:1         92   0.84*                                    50        1.25     40:1         89   0.77*                                    50        0.625    80:1         85   0.77*                                    40        20       2:1          99   2.09                                     40        10       4:1          98   1.27                                     40        7.5      5.3:1        98   1.06                                     40        5        8:1          95   0.91*                                    40        3.75    10.7:1        92   0.83*                                    40        2.5      16:1         89   0.77*                                    40        1.25     32:1         85   0.69*                                    40        0.625    64:1         82   0.67*                                    25        20      1.25:1        99   1.93                                     25        10       2.5:1        98   1.11                                     25        7.5      3.3:1        98   0.90*                                    25        5        5:1          92   0.76*                                    25        3.75     6.7:1        91   0.65*                                    25        2.5      10:1         81   0.66*                                    25        1.25     20:1         68   0.67*                                    25        0.625    40:1         57   0.71*                                    20        20       1:1          99   1.88                                     20        10       2:1          98   1.05                                     20        7.5      2.7:1        97   0.85*                                    20        5        4:1          91   0.70*                                    20        3.75    5.33:1        90   0.63*                                    20        2.5      8:1          80   0.59*                                    20        1.25     16:1         61   0.66*                                    20        0.625    32:1         49   0.70*                                    ______________________________________                                    

Asterisks in the SI column indicate synergistic combinations inaccordance with the Kull method supra. The double asterisk indicatesthat the "Belclene 350" product tested consisted of 50% (wt.) activebiocidal ingredient, and that the quat product tested consisted of 80%(wt.) active biocidal ingredient.

In Tables I and II, differences seen between the replicates are due tonormal experimental variance.

In accordance with Tables I-II supra., unexpected results occurred morefrequently within the product ratios of TPC product to quat product offrom about 2:1 to 80:1. Since the tested quat product was about 80%active, and the tested Belclene 350 product was about 50% activebiocidal ingredient, this range translates to a range of TPC:quat (100%actives basis) of about 1.25:1 to about 50:1. At present, it ispreferred that the commercial product embodying the invention comprisesa weight ratio of about 4:1, TPC:quat.

While this invention has been described with respect to particularembodiments thereof, it is apparent that numerous other forms andmodifications of this invention will be obvious to those skilled in theart. The appended claims and this invention generally should beconstrued to cover all such obvious forms and modifications which arewithin the true spirit and scope of the present invention.

We claim:
 1. A bacterial inhibiting composition comprising a synergisticaqueous mixture of (a) tri n-butyl tetradecyphosphonium chloride (TPC),and (b) n-alkyl dimethylbenzyl ammonium chloride (quat), wherein saidquat comprises an alkyl distribution of about 50% C₁₄, 40% C₁₂, and 10%C₁₆ wherein the weight ratio of said TPC to said quat is from about 2:1to 50:1.
 2. The composition as recited in claim 1 wherein the weightratio of TPC to quat is about 4:1.
 3. A method for controlling thegrowth of Klebsiella pneumoniae bacteria in an aqueous system whichcomprises adding to said system from about 0.1 to 200 parts per weightof a composition per one million parts per weight of said aqueoussystem, said composition comprising a synergistic mixture of (a) trin-butyl tetradecyl phosphonium chloride (TPC), and (b) n-alkyldimethylbenzyl ammonium chloride (quat), wherein said quat comprises analkyl distribution of about 50% C₁₄, 40% C₁₂, and 10% C₁₆ and the weightratio of TPC to quat being from abut 2:1 to 50:1.
 4. The method asrecited in claim 3 wherein the weight ratio of TPC:quat is about 4:1. 5.The method as recited in claim 3 wherein said composition is added tosaid system in an amount of from about 5 to about 50 parts per millionof said aqueous system.
 6. The method as recited in claim 3 wherein saidaqueous system comprises a cooling water system.
 7. The method asrecited in claim 3 wherein said aqueous system comprises a pulping andpapermaking system.
 8. The method as recited in claim 3 wherein saidquat is in the form of an aqueous composition comprising about 80%active biocidal ingredient, and wherein said TPC is in the form of anaqueous composition comprising about 50% active biocidal ingredient.